Migraine is a disorder that exhibits a spectrum of treatment responses in afflicted individuals. Some sufferers are fortunate and therapy may be over-the-counter remedies or even non-drug regimens using behavior modification, acupuncture, and/or hypnosis as instruments for aborting the headache. Bed rest, a darkened room, and the use of cold packs applied to the temporal artery and its branches may modify the attack. Sleep also has a beneficial effect in ending an attack. Most patients, however, will require prescription drugs for relief from the migraine. The symptoms most in need of treatment are the head pain and gastrointestinal symptoms. To a lesser degree, photophobia and the aura warrant treatment. The latter may also be quite disturbing and require treatment although its duration is relatively brief. The oral absorption of agents is less than optimal during acute migraine because of the reduced gastrointestinal peristalsis. The more severe the attack, the greater is the absorption reduced. Furthermore, the presence of nausea and frequent vomiting will preclude oral administration of pharmacological agents.
The exact pathogenesis of migraine is still unknown. Many theories have been elaborated, but none can account for all the clinical features or for all the pathophysiological aspects demonstrated in recent years. The pendulum has been swinging between vascular (Wolff 1963) and neurogenic (Sicuteri 1986) theories, with brief peripheral blood excursions (Hannington et al, 1981). In recent years, however, a general consensus has been emerging that in migraine both vascular and neural components are relevant and most probably interrelated (Lance et al, 1983; Welch 1987; Olesen 1991).
Recent epidemicologic data suggest that 17.6% of adult females and 5.7% of adult males suffer from migraine (Stewart et al, 1992). The Center for Disease Control (1991) recently reported that over the last decade the prevalence of migraine has increased by 60%. In addition, migraine is significantly under-diagnosed, with only 40% of adult females and 30% of adult males suffering from migraine being patient diagnosed (Lipton et al, 1992). Yet 80% of this population of undiagnosed patients suffering from migraine experience disability (Stewart et al, 1992), and most seek periodic medical care for other medical conditions.
Migraine is also under-treated. Only about 40% of females and 30% of males utilize prescription drugs (Celentano et al, 1992). However, many of these patients discontinue prescription medication and rely on the over-the-counter remedies.
The most common drugs, which at present are used for the treatment of migraine and other forms of vascular headaches, are e.g. triteness, ergotamine, aspirin and NSAIDS.
One major problem with the mentioned drugs is that they often have an onset time of from 60 minutes and up to 4 hours. This is a disadvantage in therapy of vascular headache conditions such a migraine.
Thus, the problem underlying the present invention is to find a new way of therapy for vascular headache conditions, and in particular migraine, with as few side effects as possible. A further problem underlying the present invention, is to find a new way of therapy providing a fast onset of action, i.e. a fast pain relief as well as relief of the symptoms associated with a vascular headache condition, to patients suffering from the vascular headache condition.
Angiotensin II (AT II) type 1 receptor antagonists are compounds which are known to interfere with the renin-angiotensin system (RAS) and are used to treat common cardiovascular diseases, particularly arterial hypertension and congestive heart failure.
Angiotensin II type 1 receptor antagonists for which the present invention has found a new medical use are thus known in the art. However, nothing has been disclosed in connection with their potential effects in prophylaxis and/or therapeutic treatment of patients suffering is from vascular headache conditions and more particularly migraine.
In Arch. Intern. Med. Vol. 160, June 2000, pp. 1654-1658, L. Hansson et al., discloses results from a double-blind, placebo-controlled study with irbesartan, of patients having mild-to-moderate hypertension. The use of irbesartan is, according to the authors, associated with a significant reduction in the incidence of headache commonly seen in hypertensive patients.
EP 456 510-A1 of Merck, discloses compounds which are said to exhibit AII antagonist activity by the IC50 assay.